A number of methods are known for masking the taste of drugs; this is an increasingly important issue in the area of patient compliance with recommended pharmaceutical therapies. As explained by M. Ueda in "Recent Pharmaceutical Techniques and Outlook for Masking the Bitter Taste of Granules," Gifu Yakuke Daigaku K.English Pound.yo 44:18-31 (1995), taste masking techniques may be broadly divided into physical, chemical, biochemical and organoleptic methods. The technique to be adopted will depend on several factors, but primarily on the extent of bitterness of the drug to be incorporated into an oral pharmaceutical formulation.
Organoleptic methods of taste-masking involve addition of a flavoring and/or sweetening agent and as such are relatively simple. However, simple addition of a taste-masking agent such as a flavoring agent or sweetener is frequently not useful by itself, unless the drug to be taste-masked is not particularly bitter. Recent biochemical methods involve the use of lipoproteins to react with bitterness receptor sites, thereby suppressing the response to the drug's bitterness. The most common masking methods, however, are based on physical means, including agglomeration, coating, and microencapsulation. Microencapsulation is essentially a process by which coatings are applied to small particles of solids, droplets of liquids or dispersions, so as to form microcapsules; the technique differs from other coating procedures in that the size of the particles generally ranges from several tenths of a .mu.m to 5000 .mu.m in diameter.
The present invention involves the use of a microencapsulation technique to taste mask drugs in an oral pharmaceutical formulation. The microencapsulation technique is a coacervation-phase separation process which involves utilization of three phases: a "core material" phase of the drug to be encapsulated; a "coating material" phase of the substance which will ultimately form the coating; and a liquid phase in which the core and coating materials are dispersed or dissolved. The coating is then deposited on the core material, and a desolvation process is used to remove the liquid phase and isolate the microcapsules. In contrast to prior microencapsulation techniques, the present invention makes use of materials and process parameters which enable preparation of uniform, impervious coatings, and involves preparation of formulations having high coating levels. In this way, the invention provides for extremely effective taste masking while also providing for release of drug shortly after the drug passes through the mouth. Generally, as will be appreciated by those working in the field, it is very unusual and quite difficult to achieve fast drug release with high coating levels effective in taste masking. The invention, having achieved these objectives, thus provides for an important advance in the art, enabling effective taste masking of a variety of drugs.